Our preliminary experiments with Borna Virus infected rats showed that this animal pathogen, native to Eastern Europe, has highly unusual pathogenic mechanisms and may be a new type of animal virus. First, the virus apparently replicates only in neural tissues, where it causes persistent infection. This makes BV virus the only obligate neural pathogen known among animal viruses. Second, inoculation of adult rats results in an immune mediated but transient encephalitis which causes lysis of neurons in the limbic system and is accompanied by bizarre behavioral disease. Third, despite persistent virus replication in brain, the encephalitis remits and lysis of neurons ceases. Frenzied behavior changes to apathy. Thus, essentially, this is a new disease with a novel pathogenesis and provides a relevant model for studying mechanisms of chronic human neurological disease characterized also by loss of selected cell populations. We propose to purify Borna virus and characterize its physical, chemical and immunological properties so that the molecular properties of the virus can be correlated with its unique biological properties. Secondly, we will investigate the mechanism of persistence of the agent in the nervous system by tracing its route of dissemination, and identifying cell targets for replication, with emphasis on those cells attacked, and those spared, by the immunologically specific, cytolytic inflammatory response. Third, the mechanism of the short lived nature of the necrotizing encephalitis will be evaluated by assessing a hypothetical role for late developing suppressor cells supplanting acute cytolytic cell responses. Lymphocytes will be cultivated from infected animals during the aggressive and passive stages of disease, cultivated in vitro, and identified in functional tests and with monoclonal antibodies. The cells will be evaluated biologically in the animal in adoptive transfer experiments. Fourth, as a followup to recent reports, we will determine, primarily in immunocytochemical tests, whether a Borna-like virus is associated with certain forms of human neurological and neuropsychiatric disease.